A continuing analysis of the biochemical effects of chemical carcinogens on their target cells is proposed. Work in the period for which support is requested will focus on the mechanisms of the lethal cell injury produced by 2 selected hepatocarcinogens, carbon tetrachloride and dimethylnitrosamine. The short-term objective is an understanding of the mechanisms underlying the liver cell necrosis produced by these agents. It is expected that this knowledge will allow steps to be taken to prevent the necrosis in the attempt to assess its role in the initiation and promotion of liver carcinogenesis. In each case, the focus of attention will be on the mechanisms of the altered calcium homeostasis produced by both agents. In the case of CC14 attention will be focused on a recently detected abnormality in the plasma membrane and its relationship to the microsomal membrane injury secondary to lipid peroxidation. In the case of DMN attention will be directed towards the effects of methylation of the plasma membrane on its structure and function.